The cytotoxicities of the
nitric oxide (NO) donors, S-nitroso-N-acetylpencillamine (SNAP) and three glyco-SNAPs, glucose-1-SNAP,
glucose-2-SNAP, and fructose-1-SNAP, towards the human gingival epithelioid S-G cell line and three human
carcinoma cell lines derived from tissues of the oral cavity were compared using the
neutral red (NR) assay. In general, the
glucose-SNAPs were more cytotoxic than SNAP, which, in turn, was more cytotoxic than fructose-1-SNAP. Further studies focused on the response of S-G cells to
glucose-2-SNAP. The cytotoxicity of
glucose-2-SNAP was attributed to NO, as
glucose-2-SNAP (t1/2=20 h at 28 degrees C) aged for 4 days was nontoxic, toxicity was eliminated in the presence of
hydroxocobalamin, a specific NO scavenger, and toxicity was not noted with glucose-2-AP (the parent compound used to construct
glucose-2-SNAP). Exposure of cells to
glucose-2-SNAP resulted in a lessening of the intracellular level of
glutathione and cells pretreated with the
glutathione-depleter, 1,3-bis-(chloroethyl)-1-nitrosourea, were more sensitive to a subsequent challenge with
glucose-2-SNAP. Cytotoxicity of
glucose-2-SNAP was lessened upon coexposure with the
antioxidants,
myricetin,
N-acetyl-L-cysteine, and
L-ascorbic acid. S-G cells exposed to
glucose-2-SNAP exhibited bi- and multinucleation. Death of S-G cells exposed to
glucose-2-SNAP apparently occurred by apoptosis, as demonstrated with fluorescence microscopy by the appearance of brightly stained, hypercondensed
chromatin in spherical cells and of membrane blebbing and by the
DNA-ladder of oligonucleosome-length fragments noted with gel electrophoresis. In comparison with other classes of NO donors the sequence of toxicity towards S-G cells was
S-nitrosoglutathione>
glucose-SNAPs>SNAP,
sodium nitroprusside>
spermine NONOate>
DPTA NONOate>
DETA NONOate>
fructose-1-SNAP>>SIN-1.